In recent years, adiponectin, which is a factor (adipokine) generally secreted from adipocytes, has been reported to have an insulin-resistance-ameliorating effect or an anti-arteriosclerotic effect (Non-Patent Document 1). Hitherto, adipokines other than adiponectin (e.g., TNF-α, resistin, and free fatty acids) are known to induce insulin resistance. Unlike the cases of many adipokines, adiponectin ameliorates insulin resistance; i.e., adiponectin is a “good” adipokine, and thus it has recently become of great interest.
Some clinical data have shown that adiponectin has the aforementioned effects and, in addition, a reduction in blood adiponectin level can be used as a marker for predicting the onset of diabetes (Non-Patent Document 2). Blood adiponectin level has been reported to be inversely correlated with the degree of obesity (Non-Patent Document 3), and adiponectin reduction has been considered to play an important role in development or exacerbation of obesity-induced insulin resistance, diabetes or cardiovascular diseases. Therefore, a substance which promotes secretion of adiponectin has been considered to be useful for preventing or ameliorating such a disease.
There have been established several in vitro test systems for measuring adiponectin expression level. For example, as has been reported, in a system in which 3T3-L1 cells (i.e., preadipocyte cell line) have been differentiated, adiponectin expression level is reduced through addition of, for example, TNF-α (tumor necrosis factor α), insulin, or dexamethason (Non-Patent Document 4).
Also, adiponectin expression level has been measured in a test system employing adipocytes isolated upon abdominal surgery (Non-Patent Document 5). As has been reported, in vitro screening of adiponectin expression inducers can be carried out by use of cells harboring an enhancer element of adiponectin and reporter gene (Patent Document 1).
In an in vivo test system, an obese diabetic animal model (e.g., KKAy mouse (Non-Patent Document 6), db/db mouse (Non-Patent Document 7), ob/ob mouse (Non-Patent Document 8), C57BL/6 mouse (Non-Patent Document 9), or Zucker fatty (Non-Patent Document 10)) has been used for evaluating, for example, adiponectin secretion ability, since such an obese diabetic animal model develops obesity, insulin resistance, hypertriglyceridemia, or the like under high-fat diet, and the animal model shows a reduction in blood adiponectin level in association with obesity.
However, such a test system poses problems in that the test system requires a long period of time for evaluating change in amount of adiponectin secreted in an animal model, since the animal model must be reared under high-fat diet for at least several weeks until blood adiponectin level is reduced in the animal model.